The work is directed toward the design of compounds, in particular nucleotide derivatives, which would irreversibly inhibit an enzyme isolated from neoplastic tissue without affecting the substrate-identical enzyme isolated from normal host tissue. In a systematic approach toward such tumor tissue-specific irreversible enzyme inhibitors, the contact points of nucleotide substrates with candidate enzymes will be determined by removal of or substitution on probable binding atoms of the substrate, after which bulk tolerance within enzyme-substrate complexes will be investigated by the introduction of small groups at various positions on the substrates. Side chains bearing electrophilic groups will then be attached at atoms of the substrate which are in areas of bulk tolerance.